The present invention relates to novel imidazole derivatives exhibiting cytokine-like activities; in particular, activities analogous to those exhibited by granulocyte-colony stimulating factor (hereinafter referred to as xe2x80x9cG-CSFxe2x80x9d).
G-CSF drugs have been found effective in therapy of immune diseases which accompany reduction in neutrophils caused by chemotherapy or radiotherapy of cancer. In clinical settings, a human gene recombinant G-CSF injection (Sankyo Co., Ltd.) or similar products are currently employed as G-CSF drugs. However, the G-CSF injection involves drawbacks; namely, it produces problematic side effects, such as inflammation, bone pain, fever, and chill, and upon oral administration it is rapidly degraded, because it is composed of glycoproteins. Therefore, in order to solve these problems, there remains need for development of a low-molecular weight compound which exhibits G-CSF-like activity and which can serve as a substitute for G-CSF drugs. However, presently, very few compounds, such as those described in WO97/44033, are known to exhibit G-CSF-like activities.
Accordingly, an object of the present invention is to provide a novel low-molecular-weight compound exhibiting cytokine-like activities, particularly G-CSF-like activities.
Numerous studies have been carried out on imidazole compounds for possible application as agrochemicals or pharmaceuticals. Of the imidazole compounds, those having a 2-alkoxyphenyl group are reported in Japanese Patent Application Laid-Open (kokai) Nos. 63-146864 or 61-267557. However, these publications fail to mention whether or not those compounds exhibit cytokine-like activities. Moreover, a 2-alkoxyphenyl derivative having a halogen group at the 5-position of the phenyl group has not yet been reported.
Under the above circumstances, the present inventors performed screening tests on a variety of compounds, in search of low-molecular-weight compound having G-CSF-like activities, and have found that a novel class of imidazole derivatives (1) having a 2-alkoxy-5-halogenophenyl group exhibits cytokine-like activities; in particular, G-CSF-like activities, thus leading to completion of the invention.
The present invention provides an imidazole derivative represented by the following formula (1): 
(wherein R1 represents a lower alkyl group, R2 represents an alkyl or aralkyl group, and X1 represents a halogen atom) or a salt thereof, and an intermediate for the synthesis of the derivative or the salt.
The present invention also provides a drug containing an imidazole derivative of formula (1) or a salt thereof as an active ingredient.
The present invention also provides a pharmaceutical composition containing an imidazole derivative of formula (1) or a salt thereof, and a pharmacologically acceptable carrier.
The present invention also provides use of an imidazole derivative of formula (1) or a salt thereof in manufacture of a drug.
The present invention further provides a method of treating an immune disease accompanying reduction in neutrophils, the method comprising administration of an imidazole derivative of formula (1) to a patient in need thereof.